Mucorales are basal fungi that opportunistically cause a potentially fatal infection known as mucormycosis (black fungus disease), which poses a significant threat to human health due to its high mortality rate and its recent association with SARS-CoV-2 infections. On the other hand, histone methylation is a regulatory mechanism with pleiotropic effects, including the virulence of several pathogenic fungi. However, the role of epigenetic changes at the histone level never has been studied in Mucorales. Here, we dissected the functional role of Set1, a histone methyltransferase that catalyzes the methylation of H3K4, which is associated with the activation of gene transcription and virulence. A comparative analysis of the Mucor lusitanicus genome (previously known as Mucor circinelloides f. lusitanicus) identified only one homolog of Set1 from Candida albicans and Saccharomyces cerevisiae that contains the typical SET domain. Knockout strains in the gene set1 lacked H3K4 monomethylation, dimethylation, and trimethylation enzymatic activities. These strains also showed a significant reduction in vegetative growth and sporulation. Additionally, set1 null strains were more sensitive to SDS, EMS, and UV light, indicating severe impairment in the repair process of the cell wall and DNA lesions and a correlation between Set1 and these processes. During pathogen-host interactions, strains lacking the set1 gene exhibited shortened polar growth within the phagosome and attenuated virulence both in vitro and in vivo. Our findings suggest that the histone methyltransferase Set1 coordinates several cell processes related to the pathogenesis of M. lusitanicus and may be an important target for future therapeutic strategies against mucormycosis.
Background: Chromoblastomycosis is the World Health Organization (WHO)-recognized fungal implantation disease that eventually leads to severe mutilation. Cladophialophora carrionii (C. carrionii) is one of the agents. However, the pathogenesis of C. carrionii is not fully investigated yet.
Methods: We investigated the pathogenic potential of the fungus in a Galleria mellonella (G. mellonella) larvae infection model. Six strains of C. carrionii, and three of its environmental relative C. yegresii were tested. The G. mellonella model was also applied to determine antifungal efficacy of amphotericin B, itraconazole, voriconazole, posaconazole, and terbinafine.
Results: All strains were able to infect the larvae, but virulence potentials were strain-specific and showed no correlation with clinical background of the respective isolate. Survival of larvae also varied with infection dose, and with growth speed and melanization of the fungus. Posaconazole and voriconazole exhibited best activity against Cladophialophora, followed by itraconazole and terbinafine, while limited efficacy was seen for amphotericin B.
Conclusion: Infection behavior deviates significantly between strains. In vitro antifungal susceptibility of tested strains only partly explained the limited treatment efficacy in vivo.
Members of the genus Cryptococcus are the causative agents of cryptococcal meningitis, a disease mainly associated with HIV-induced immunosuppression. Patients with cryptococcal meningitis are at a serious risk of death. Most patients suffering from cryptococcosis belong to neglected populations. With reduced support for research, new therapies are unlikely to emerge. In this essay, we used the Policy Cures/G-finder platform as a reference database for funding research on cryptococcal disease. Funding for cryptococcal research started being tracked by G-finder in 2013 and has continued to appear in the annual reports ever since. In total, 15 institutions were reported as major funders for research on cryptococcal disease over the years. The US National Institutes of Health (NIH) was the main funder, followed by the UK's Wellcome Trust. The annual analysis suggested slow yearly growth in funding from 2013 to 2021. The development of new tools to prevent and fight cryptococcal disease is urgent but requires improved funding.
Rust fungi (Pucciniales, Basidiomycota) are a species-rich (ca. 8000 species), globally distributed order of obligate plant pathogens. Rust species are host-specific, and as a group they cause disease on many of our most economically and/or ecologically significant plants. As such, the ability to accurately and rapidly identify these fungi is of particular interest to mycologists, botanists, agricultural scientists, farmers, quarantine officials, and associated stakeholders. However, the complexities of the rust life cycle, which may include production of up to five different spore types and alternation between two unrelated host species, have made standard identifications, especially of less-documented spore states or alternate hosts, extremely difficult. The Arthur Fungarium (PUR) at Purdue University is home to one of the most comprehensive collections of rust fungi in the world. Using material vouchered in PUR supplemented with fresh collections we generated DNA barcodes of the 28S ribosomal repeat from > 3700 rust fungal specimens. Barcoded material spans 120 genera and > 1100 species, most represented by several replicate sequences. Barcodes and associated metadata are hosted in a publicly accessible, BLAST searchable database called Rust HUBB (Herbarium-based Universal Barcode Blast) and will be continuously updated.
Ophiocordyceps sinensis is a famous traditional Chinese medicine adapted to the alpine environment of the Qinghai-Tibet Plateau and adjacent regions. Clarification of the species diversity of Ophiocordyceps sinensis and its relatives could expand the traditional medicinal resources and provide insights into the speciation and adaptation. The study is prompted by the discovery of a new species, O. megala, described here from a biodiversity hotspot in the Hengduan Mountains, China. Combined morphological, ecological, and phylogenetic evidence supports its distinctiveness from O. sinensis, O. xuefengensis, and O. macroacicularis. Additionally, based on the phylogenetic construction of Ophiocordyceps, a special clade was focused phylogenetically on the more closely related O. sinensis complex, which was defined as the O. sinensis- species complex lineage. A total of 10 species were currently confirmed in this lineage. We made a comprehensive comparison of the sexual/asexual morphological structures among this species complex, distinguishing their common and distinctive features. Furthermore, using the method of species distribution modelling, we studied the species ocurrences in relation to climatic, edaphic, and altitudinal variables for the eight species in the O. sinensis-species complex, and determined that their potential distribution could extend from the southeastern Qinghai-Tibet Plateau to the Xuefeng Mountains without isolating barrier. Thus, the biodiversity corridor hypothesis was proposed around the O. sinensis-species complex. Our study highlights the phylogeny, species diversity, and suitable distribution of the O. sinensis-species complex lineage, which should have a positive implication for the resource discovery and adaptive evolution of this unique and valuable group.
Emerging fungal pathogens are a global challenge for humankind. Many efforts have been made to understand the mechanisms underlying pathogenicity in bacteria, and OMICs techniques are largely responsible for those advancements. By contrast, our limited understanding of opportunism and antifungal resistance is preventing us from identifying, limiting and interpreting the emergence of fungal pathogens. The genus Scedosporium (Microascaceae) includes fungi with high tolerance to environmental pollution, whilst some species can be considered major human pathogens, such as Scedosporium apiospermum and Scedosporium boydii. However, unlike other fungal pathogens, little is known about the genome evolution of these organisms. We sequenced two novel genomes of Scedosporium aurantiacum and Scedosporium minutisporum isolated from extreme, strongly anthropized environments. We compared all the available Scedosporium and Microascaceae genomes, that we systematically annotated and characterized ex novo in most cases. The genomes in this family were integrated in a Phylum-level comparison to infer the presence of putative, shared genomic traits in filamentous ascomycetes with pathogenic potential. The analysis included the genomes of 100 environmental and clinical fungi, revealing poor evolutionary convergence of putative pathogenicity traits. By contrast, several features in Microascaceae and Scedosporium were detected that might have a dual role in responding to environmental challenges and allowing colonization of the human body, including chitin, melanin and other cell wall related genes, proteases, glutaredoxins and magnesium transporters. We found these gene families to be impacted by expansions, orthologous transposon insertions, and point mutations. With RNA-seq, we demonstrated that most of these anciently impacted genomic features responded to the stress imposed by an antifungal compound (voriconazole) in the two environmental strains S. aurantiacum MUT6114 and S. minutisporum MUT6113. Therefore, the present genomics and transcriptomics investigation stands on the edge between stress resistance and pathogenic potential, to elucidate whether fungi were pre-adapted to infect humans. We highlight the strengths and limitations of genomics applied to opportunistic human pathogens, the multifactoriality of pathogenicity and resistance to drugs, and suggest a scenario where pressures other than anthropic contributed to forge filamentous human pathogens.
Thermotolerance in Mucorales (Mucoromycotina) is one of the factors to be opportunistic pathogens, causing mucormycosis. Among thermotolerant mucoralean fungi, Burkholderiaceae-related endobacteria (BRE) are rarely found and the known range of hosts is limited to Rhizopus spp. The phylogenetic divergence of BRE has recently expanded in other fungal groups such as Mortierellaceae spp. (Mortierellomycotina); however, it remains unexplored in Mucorales. Here, we found a thermotolerant mucoralean fungus obtained from a litter sample collected from Haha-jima Island in the Ogasawara (Bonin) Islands, Japan. The fungus was morphologically, phylogenetically, and physiologically characterized and proposed as a new species, Saksenaea boninensis sp. nov. Besides the fungal taxonomy, we also found the presence of BRE in isolates of this species by diagnostic PCR amplification of the 16S rRNA gene from mycelia, fluorescence microscopic observations, and isolation of the bacterium in pure culture. Phylogenetic analysis of the 16S rRNA gene of BRE revealed that it is distinct from all known BRE. The discovery of a culturable BRE lineage in the genus Saksenaea will add new insight into the evolutional origin of mucoralean fungus-BRE associations and emphasize the need to pay more attention to endofungal bacteria potentially associated with isolates of thermotolerant mucoralean fungi causing mucormycosis.